tbuckley/cabot-search huggingface dataset:
Hnf4 activates mimetic-cell enhancers to recapitulate gut and liver development within the thymus
Authors: Daniel A. Michelson, Chong Zuo, Michael Verzi, Christophe Benoist, Diane Mathis
Journal: The Journal of Experimental Medicine (2023)

Mimetic cells are medullary thymic epithelial cells (mTECs) that mimic extra-thymic cell types to tolerize T cells to self-antigens. Here, we dissected the biology of entero-hepato mTECs, mimetic cells expressing gut- and liver-associated transcripts. Entero-hepato mTECs conserved their thymic identity yet accessed wide swaths of enterocyte chromatin and transcriptional programs via the transcription factors Hnf4α and Hnf4γ. Deletion of Hnf4α and Hnf4γ in TECs ablated entero-hepato mTECs and downregulated numerous gut- and liver-associated transcripts, with a primary contribution from Hnf4γ. Loss of Hnf4 impaired enhancer activation and CTCF redistribution in mTECs but did not impact Polycomb-mediated repression or promoter-proximal histone marks. By single-cell RNA sequencing, Hnf4 loss produced three distinct effects on mimetic cell state, fate, and accumulation. Serendipitously, a requirement for Hnf4 in microfold mTECs was discovered, which exposed a requirement for Hnf4γ in gut microfold cells and the IgA response. Study of Hnf4 in entero-hepato mTECs thus revealed mechanisms of gene control in the thymus and periphery alike.
Long-Term Implications of Using Screen Time to Guide Care
Authors: Barry R. Bryant, Joseph F. McGuire
Journal: JAMA Pediatrics (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Stepwise Evolution of <i>E. coli</i> C and ΦX174 Reveals Unexpected Lipopolysaccharide (LPS) Diversity
Authors: Jordan Romeyer Dherbey, Lavisha Parab, Jenna Gallie, Frederic Bertels
Journal: Molecular Biology and Evolution (2023)

Abstract Phage therapy is a promising method for the treatment of multidrug-resistant bacterial infections. However, its long-term efficacy depends on understanding the evolutionary effects of the treatment. Current knowledge of such evolutionary effects is lacking, even in well-studied systems. We used the bacterium Escherichia coli C and its bacteriophage ΦX174, which infects cells using host lipopolysaccharide (LPS) molecules. We first generated 31 bacterial mutants resistant to ΦX174 infection. Based on the genes disrupted by these mutations, we predicted that these E. coli C mutants collectively produce eight unique LPS structures. We then developed a series of evolution experiments to select for ΦX174 mutants capable of infecting the resistant strains. During phage adaptation, we distinguished two types of phage resistance: one that was easily overcome by ΦX174 with few mutational steps (“easy” resistance) and one that was more difficult to overcome (“hard” resistance). We found that increasing the diversity of the host and phage populations could accelerate the adaptation of phage ΦX174 to overcome the hard resistance phenotype. From these experiments, we isolated 16 ΦX174 mutants that, together, can infect all 31 initially resistant E. coli C mutants. Upon determining the infectivity profiles of these 16 evolved phages, we uncovered 14 distinct profiles. Given that only eight profiles are anticipated if the LPS predictions are correct, our findings highlight that the current understanding of LPS biology is insufficient to accurately forecast the evolutionary outcomes of bacterial populations infected by phage.
Two‐year results of tapered dupilumab for CRSwNP demonstrates enduring efficacy established in the first 6 months
Authors: Rik Johannes Leonardus van der Lans, Josje Janna Otten, Gwijde Flavius Jacobus Petrus Maria Adriaensen, Dinand Rienk Hoven, Linda Berendina Benoist, Wytske Johanna Fokkens, Sietze Reitsma
Journal: Allergy (2023)

Dupilumab is an anti-T2-inflammatory biological registered for chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), indicated by integrated CRS-care pathways when optimal medico-surgical treatment yields insufficient CRS control. This study aims to evaluate long-term results with focus on established therapeutic efficacy while tapering dupilumab.Real-life, prospective observational cohort study in single tertiary referral center with add-on dupilumab as primary biological treatment in adult (≥18 years) biological-naïve CRSwNP patients per the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS)2020-indication with a 2-year follow-up. Tapering (increasing interdose interval) applied every 24 weeks, conditional to sufficient treatment response and CRS control.Mean scores (s.d.) of all co-primary outcomes improved significantly from baseline ( 228) to the 48 ( 214) and 96-weeks ( 99) timepoints: Nasal Polyp Score (0-8) improved from 5,3 (1,9) to 1,4 (1,8) and 1,3 (1,7); SinoNasal Outcome Test (SNOT)-22 (0-110) improved from 53,6 (19,6) to 20,2 (15,4) and 21,2 (15,6); Sniffin'Sticks-12 identification test (0-12; 0-6 anosmia, 7-10 hyposmia, 11-12 normosmia) improved from 3,7 (2,4) to 7,7 (2,9) and 7,3 (3,04); Asthma Control Test (5-25; >19 indicating well-controlled asthma) improved from 18,5 (4,8) to 21,8 (3,8) and 21,4 (3,9). Tapering was feasible in 79,5% of the patients at the 24-weeks timepoint, and in 93,7% and 95,8% at the 48- and 96-weeks timepoints, respectively. One-way repeated-measures ANOVA demonstrated no significant alterations of individual co-primary outcome mean-scores from 24 weeks onward.This first long-term real-life prospective observational cohort study shows high therapeutic efficacy of dupilumab for severe CRswNP in the first 2 years. Therapeutic efficacy is principally established within 24 weeks and endures while tapering dupilumab conditional to treatment response and CRS control.
Trends in State-Level Maternal Mortality by Racial and Ethnic Group in the United States
Authors: Laura G. Fleszar, Allison S. Bryant, Catherine O. Johnson, Brigette F. Blacker, Aleksandr Aravkin, Mathew Baumann, Laura Dwyer-Lindgren, Yekaterina O. Kelly, Kelsey Maass, Peng Zheng, Gregory A. Roth
Journal: JAMA (2023)

Importance Evidence suggests that maternal mortality has been increasing in the US. Comprehensive estimates do not exist. Long-term trends in maternal mortality ratios (MMRs) for all states by racial and ethnic groups were estimated. Objective To quantify trends in MMRs (maternal deaths per 100 000 live births) by state for 5 mutually exclusive racial and ethnic groups using a bayesian extension of the generalized linear model network. Design, Setting, and Participants Observational study using vital registration and census data from 1999 to 2019 in the US. Pregnant or recently pregnant individuals aged 10 to 54 years were included. Main Outcomes and Measures MMRs. Results In 2019, MMRs in most states were higher among American Indian and Alaska Native and Black populations than among Asian, Native Hawaiian, or Other Pacific Islander; Hispanic; and White populations. Between 1999 and 2019, observed median state MMRs increased from 14.0 (IQR, 5.7-23.9) to 49.2 (IQR, 14.4-88.0) among the American Indian and Alaska Native population, 26.7 (IQR, 18.3-32.9) to 55.4 (IQR, 31.6-74.5) among the Black population, 9.6 (IQR, 5.7-12.6) to 20.9 (IQR, 12.1-32.8) among the Asian, Native Hawaiian, or Other Pacific Islander population, 9.6 (IQR, 6.9-11.6) to 19.1 (IQR, 11.6-24.9) among the Hispanic population, and 9.4 (IQR, 7.4-11.4) to 26.3 (IQR, 20.3-33.3) among the White population. In each year between 1999 and 2019, the Black population had the highest median state MMR. The American Indian and Alaska Native population had the largest increases in median state MMRs between 1999 and 2019. Since 1999, the median of state MMRs has increased for all racial and ethnic groups in the US and the American Indian and Alaska Native; Asian, Native Hawaiian, or Other Pacific Islander; and Black populations each observed their highest median state MMRs in 2019. Conclusion and Relevance While maternal mortality remains unacceptably high among all racial and ethnic groups in the US, American Indian and Alaska Native and Black individuals are at increased risk, particularly in several states where these inequities had not been previously highlighted. Median state MMRs for the American Indian and Alaska Native and Asian, Native Hawaiian, or Other Pacific Islander populations continue to increase, even after the adoption of a pregnancy checkbox on death certificates. Median state MMR for the Black population remains the highest in the US. Comprehensive mortality surveillance for all states via vital registration identifies states and racial and ethnic groups with the greatest potential to improve maternal mortality. Maternal mortality persists as a source of worsening disparities in many US states and prevention efforts during this study period appear to have had a limited impact in addressing this health crisis.
Current and Future Challenges Regarding Estimating Costs to Determine the Value of Interventions to Manage Unhealthy Weight
Authors: Andrea Luviano, Ankur Pandya, Davene R. Wright
Journal: JAMA Pediatrics (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Greed in US Health Care—Reply
Authors: Donald M. Berwick
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Evolutionary Shortcuts via Multinucleotide Substitutions and Their Impact on Natural Selection Analyses
Authors: Alexander G Lucaci, Jordan D Zehr, David Enard, Joseph W Thornton, Sergei L Kosakovsky Pond
Journal: Molecular Biology and Evolution (2023)

Abstract Inference and interpretation of evolutionary processes, in particular of the types and targets of natural selection affecting coding sequences, are critically influenced by the assumptions built into statistical models and tests. If certain aspects of the substitution process (even when they are not of direct interest) are presumed absent or are modeled with too crude of a simplification, estimates of key model parameters can become biased, often systematically, and lead to poor statistical performance. Previous work established that failing to accommodate multinucleotide (or multihit, MH) substitutions strongly biases dN/dS-based inference towards false-positive inferences of diversifying episodic selection, as does failing to model variation in the rate of synonymous substitution (SRV) among sites. Here, we develop an integrated analytical framework and software tools to simultaneously incorporate these sources of evolutionary complexity into selection analyses. We found that both MH and SRV are ubiquitous in empirical alignments, and incorporating them has a strong effect on whether or not positive selection is detected (1.4-fold reduction) and on the distributions of inferred evolutionary rates. With simulation studies, we show that this effect is not attributable to reduced statistical power caused by using a more complex model. After a detailed examination of 21 benchmark alignments and a new high-resolution analysis showing which parts of the alignment provide support for positive selection, we show that MH substitutions occurring along shorter branches in the tree explain a significant fraction of discrepant results in selection detection. Our results add to the growing body of literature which examines decades-old modeling assumptions (including MH) and finds them to be problematic for comparative genomic data analysis. Because multinucleotide substitutions have a significant impact on natural selection detection even at the level of an entire gene, we recommend that selection analyses of this type consider their inclusion as a matter of routine. To facilitate this procedure, we developed, implemented, and benchmarked a simple and well-performing model testing selection detection framework able to screen an alignment for positive selection with two biologically important confounding processes: site-to-site synonymous rate variation, and multinucleotide instantaneous substitutions.
Maternal Hepatitis B Virus Infection and Risk of Congenital Heart Diseases—Reply
Authors: Hanbin Wu, Ying Yang, Xu Ma
Journal: JAMA Pediatrics (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Extracellular aaRSs drive autoimmune and inflammatory responses in rheumatoid arthritis via the release of cytokines and PAD4
Authors: Akihiro Kimura, Takeshi Takagi, Thiprampai Thamamongood, Satoshi Sakamoto, Takumi Ito, Iwao Seki, Masahiro Okamoto, Hiroyuki Aono, Satoshi Serada, Tetsuji Naka, Hiroaki Imataka, Kensuke Miyake, Takuya Ueda, Miki Miyanokoshi, Keisuke Wakasugi, Noriko Iwamoto, Norio Ohmagari, Takahiro Iguchi, Takeshi Nitta, Hiroshi Takayanagi, Hiroyuki Yamashita, Hiroshi Kaneko, Haruka Tsuchiya, Keishi Fujio, Hiroshi Handa, Harumi Suzuki
Journal: Annals of the Rheumatic Diseases (2023)

Recent studies demonstrate that extracellular-released aminoacyl-tRNA synthetases (aaRSs) play unique roles in immune responses and diseases. This study aimed to understand the role of extracellular aaRSs in the pathogenesis of rheumatoid arthritis (RA).Primary macrophages and fibroblast-like synoviocytes were cultured with aaRSs. aaRS-induced cytokine production including IL-6 and TNF-α was detected by ELISA. Transcriptomic features of aaRS-stimulated macrophages were examined using RNA-sequencing. Serum and synovial fluid (SF) aaRS levels in patients with RA were assessed using ELISA. Peptidyl arginine deiminase (PAD) 4 release from macrophages stimulated with aaRSs was detected by ELISA. Citrullination of aaRSs by themselves was examined by immunoprecipitation and western blotting. Furthermore, aaRS inhibitory peptides were used for inhibition of arthritis in two mouse RA models, collagen-induced arthritis and collagen antibody-induced arthritis.All 20 aaRSs functioned as alarmin; they induced pro-inflammatory cytokines through the CD14-MD2-TLR4 axis. Stimulation of macrophages with aaRSs displayed persistent innate inflammatory responses. Serum and SF levels of many aaRSs increased in patients with RA compared with control subjects. Furthermore, aaRSs released PAD4 from living macrophages, leading to their citrullination. We demonstrate that aaRS inhibitory peptides suppress cytokine production and PAD4 release by aaRSs and alleviate arthritic symptoms in a mouse RA model.Our findings uncovered the significant role of aaRSs as a novel alarmin in RA pathogenesis, indicating that their blocking agents are potent antirheumatic drugs.
Early-stage measurable residual disease dynamics and IGHV repertoire reconstitution during venetoclax and obinutuzumab treatment in chronic lymphocytic leukemia
Authors: P. J. Hengeveld, J. Schilperoord-Vermeulen, M. Y. van der Klift, J. M. N. Dubois, P. M. Kolijn, F. G. Kavelaars, M. Rijken, J. A. Dobber, K. Nasserinejad, S. Kersting, P. E. Westerweel, A. P. Kater, A. W. Langerak, M-D. Levin
Journal: Blood Cancer Journal (2023)
Antibody responses to dietary antigens are accompanied by specific plasma cells in the infant thymus
Authors: Hector Cordero, Jacob Hess, Elio Nitschki, Evgeny Kanshin, Poulomi Roy, Ronzon Shihab, David M. Kalfa, Emile A. Bacha, Beatrix Ueberheide, Emmanuel Zorn
Journal: Journal of Allergy and Clinical Immunology (2023)
When I use a word . . . Medical slang: a taxonomy
Authors: Jeffrey K Aronson
Journal: BMJ (2023)

My collection of upwards of 3000 terms of medical jargon, slang, colloquialisms, and cant can be classified under different headings: abbreviations (shortenings, initialisms, contractions, and acronyms); anthropomorphisms; borrowings from other forms of slang; compounding of different words into single phrases; euphemisms; references to historical, legendary, and fictional characters; metaphors; metonymy; ordinary words given extraordinary meanings; paronomasia; portmanteau words; rhymes; suffixes; technical terms turned into slang; and toponyms.
pH Switchable Nanozyme Platform for Healing Skin Tumor Wound Infected with Drug‐Resistant Bacteria
Authors: Yong Yan, Mengqi Wang, Minyang Zhao, Jing Zhang, Yaqing Liu, Xia Gao
Journal: Advanced Healthcare Materials (2023)

Abstract Nanozymes capable of generating reactive oxygen species have recently emerged as promising treatments for wounds infected with drug‐resistant bacteria, possessing a reduced possibility of inducing resistance. However, the therapeutic effect is limited by a shortage of endogenous oxy‐substrates and undesirable off‐target biotoxicity. Herein, a ferrocenyl coordination polymer (FeCP) nanozyme, featuring pH switchable peroxidase (POD)‐ and catalase (CAT)‐like activity is incorporated with indocyanine green (ICG) and calcium peroxide (CaO 2 ) to fabricate an H 2 O 2 /O 2 self‐supplying system (FeCP/ICG@CaO 2 ) for precise treatment of bacterial infections. At the wound site, CaO 2 reacts with water to generate H 2 O 2 and O 2 . Acting as a POD mimic under an acidic bacterial microenvironment, FeCP catalyzes H 2 O 2 into hydroxyl radicals to prevent infection. However, FeCP switches to CAT‐like activity in neutral tissue, decomposing H 2 O 2 into H 2 O and O 2 to prevent oxidative damage and facilitate wound healing. Additionally, FeCP/ICG@CaO 2 shows photothermal therapy capability, as ICG can emit heat under near‐infrared laser irradiation. This heat assists FeCP in fully exerting its enzyme‐like activity. Thus, this system achieves an antibacterial efficiency of 99.8% in vitro for drug‐resistant bacteria, and effectively overcomes the main limitations of nanozyme‐based treatment assays, resulting in satisfactory therapeutic effects in repairing normal and special skin tumor wounds infected with drug‐resistant bacteria.
The protective association of HLA-B∗52:01, HLA-C∗12:02, and DQB1∗06:01 alleles with severe acute hepatitis of unknown origin in Japanese children
Authors: Tatsuya Okamoto, Hideaki Okajima, Eri Ogawa, Kimiko Yurugi, Etsuro Hatano
Journal: Journal of Hepatology (2023)
Personalised management of patients with hepatocellular carcinoma: a multiparametric therapeutic hierarchy concept
Authors: Alessandro Vitale, Giuseppe Cabibbo, Massimo Iavarone, Luca Viganò, David J Pinato, Francesca Romana Ponziani, Quirino Lai, Andrea Casadei-Gardini, Ciro Celsa, Giovanni Galati, Martina Gambato, Laura Crocetti, Matteo Renzulli, Edoardo G Giannini, Fabio Farinati, Franco Trevisani, Umberto Cillo, Umberto Baccarani, Giuseppina Brancaccio, Raffaele Cozzolongo, Alessandro Cucchetti, Nicoletta De Matthaeis, Stefano Di Sandro, Simone Famularo, Michele Finotti, Francesco G Foschi, Davide Ghinolfi, Marco Guarracino, Salvatore Gruttadauria, Maria Guarino, Alba Kostandini, Ilaria Lenci, Giovanni B Levi Sandri, Tommaso M Manzia, Giovanni Marasco, Mario Masarone, Chiara Mazzarelli, Fabio Melandro, Luca Miele, Filomena Morisco, Daniele Nicolini, Duilio Pagano, Filippo Pelizzaro, Giulia Pieri, Fabio Piscaglia, Maria Corina Plaz Torres, Riccardo Pravisani, Maria Rendina, Fabrizio Romano, Francesco P Russo, Rodolfo Sacco, Angelo Sangiovanni, Carlo Sposito, Raffaella Tortora, Francesco Tovoli, Mauro Viganò, Paola Violi
Journal: The Lancet Oncology (2023)